Tetraphase Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company focused on next-generation antibiotics, announced today that it is presenting new results of several studies designed to support the continued advancement of its lead antibiotic, TP-434, a potent new broad-spectrum intravenous (I.V.) antibiotic with oral stepdown potential effective against difficult-to-treat and multidrug-resistant pathogens. Tetraphase also is presenting results of pre-clinical evaluations of TP-2758, the company's second novel antibiotic, which is an oral agent for complicated urinary tract infections (cUTI). These data were described in an oral podium presentation and four poster presentations at the 21st European Congress of Clinical Microbiology and Infectious Disease (ECCMID) in Milan, Italy.
"We continue to expand our data set, in both preclinical models and human studies, confirming the robust efficacy and dosing flexibility of our lead compounds - in oral and I.V. formulations - against multi-drug resistant bacterial pathogens," said Guy Macdonald, President and Chief Executive Officer. "In an effort to deliver solutions to the global health crisis caused by antibiotic resistance, we are applying these insights to the refinement of our mid- stage clinical program for TP-434 for complicated intra-abdominal infections and to the design of an efficient clinical pathway for TP-2758 as a treatment for cUTIs."
Data Summary:
- "Broad-spectrum fluorocycline TP-434 has oral bioavailability in humans." A. Leighton, I. Zupanets, N. Bezugla, L. Plamondon, G. Macdonald, J. Sutcliffe - Presented as a poster (#1509) on Monday, May 9: In results from a double-blind, placebo-controlled, single-ascending dose study in healthy men and women, TP-434 showed promising oral bioavailability, reaching exposures predicted to be therapeutically efficacious without producing serious adverse events. This study confirmed the feasibility of development of an oral formulation of TP-434.
- "The novel broad-spectrum fluorocycline TP-434 is active against MDR Gram-negative pathogens." C. Fyfe, T. Grossman, W. O'Brien, C. Achorn, J. Sutcliffe - Presented as a poster (#1149) on Sunday, May 8: TP434 showed superior in vitro activity versus clinical comparators, including tigecyline, against important multi-drug resistant gram-negative pathogens such as Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBL+) and/or carbapenamases, MDR Acinetobacter baumannii, and anaerobic bacteria such as Bacteroides fragilis. These findings support the continued development of TP-434 in Phase II clinical trials for complicated intra-abdominal infections.
- "The effects of varying susceptibility test parameters on TP-434 activity in vitro." C. Pillar, D.H. Sahm, T. Grossman, J. Sutcliffe - Presented as a poster (#762) on Saturday, May 7: The in vitro antibacterial activity of TP-434 was shown to be largely unaffected by media age and media additives, unlike tigecycline, in an evaluation of the impact of variations in in vitro susceptibility test parameters.
- "TP-2758 is a novel oral tetracycline targeting complicated urinary tract infections and pyelonephritis." J. Sutcliffe, Y. Deng, M. Ronn, X. Xiao - Presented as an oral presentation (#96) on Saturday, May 7: TP-2758 showed promising oral bioavailability in two animal species (rat and monkey) and oral antimicrobial activity equivalent to I.V. meropenem in a mouse urinary tract infection (UTI)/kidney infection model.
- "In vitro activity of TP-2758 against panels of recent bacterial clinical isolates." T. Grossman, W. O'Brien, C. Fyfe, C. Sun, W. Zhang, J. Sutcliffe - Presented as a poster (#1142) on Sunday, May 8: TP-2758 demonstrated two- to four-fold greater in vitro potency against important gram-negative pathogens, including Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBL+), than tigecycline. TP-2758 was two- to 32-fold less active against gram-positive pathogens than tigecycline.
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